The proposed research "Aging in prosimian primate: model for AD pathology" is based on the finding that several possibly related syndromes occur during CNS aging in the prosimian primate species of Otolemur. These include: central cholinergic dystrophy, beta-amyloidosis (plaques and vascular amyloid), and central acute phase response (activated microglia and elevated interleukin-1 levels). In addition, these animals manifest spontaneously in captivity dietary iron overload syndrome and mild copper deficiency which may be associated with CNS aging pathology. The specific aims are: SPECIFIC AIM 1: To test a series of Otolemurs of various ages for the attributes of copper deficiency in peripheral tissues and CNS, and to correlate iron and copper status with abnormalities in acute phase proteins (ceruloplasmin and beta-amyloid protein), abnormality in central noradrenergic and cholinergic pathways, appearance of beta-amyloidosis (vascular and plaque), and abnormalities in central immune mechanisms (gliosis, interleukin levels, and activation of microglia). SPECIFIC AIM 2: To test whether all prosimians with DIOS have 'chronic' acute phase response and the relationship to copper deficiency; and to see whether chronic stimulation of acute phase response produces a stepwise increase in CNS injury. SPECIFIC AIM 3: To test the longterm effect of altering trace mineral balance, and of protective drug regimens to CNS injury in cohorts of young Otolemur and other prosimians followed for 4-5 years to the age where CNS injury is evident in 'normal' captive Otolemur. The goal of the proposed research is to describe the relationship between peripheral abnormalities and central nervous system aging in Otolemur. Understanding the temporal sequence and cellular basis of these aging changes may further rational prevention and treatment. Vulnerability to age-related CNS injury in Otolemur may be pertinent to mechanisms n human aging and diseases with AD pathology.